Objective: This study aimed to quantitatively and qualitatively examine breast cancer screening practices, including breast self-examination (BSE), and health literacy among patients with chronic disease. Design: A prospective, multi-method study conducted with a targeted purposive sample of 297 patients with diabetes and/or hypertension from four ethnic groups (Latino, Vietnamese, African American, White-American) at an urban community health center. Setting: A federally qualified health center in Western Massachusetts. Methods: In our four-year study, 297 participants completed cancer knowledge, beliefs, attitudes and screening utilization scales and measures of health literacy. In addition to survey data collection, we conducted in-depth interviews, focus groups, home visits, and chronic disease diaries ("n" = 71). Results: In focus groups, African American, Vietnamese and Latina participants offered interviewers an unprompted demonstration of BSE, reported regular BSE use at particular times of the month, and shared positive feelings about the screening method. In a sample where approximately 93% of women have had a mammogram, many also had performed BSE (85.2%). Women with adequate health literacy were more likely than those with inadequate health literacy to rely on it. Despite being positively inclined toward BSE, Vietnamese women, who had the lowest health literacy scores in our sample, were less likely to perform BSE regularly. Conclusions: BSE seemed to be an appealing self-care practice for many women in our study, but we conclude that proper BSE practices may not be reinforced equally across ethnic groups and among patients with low health literacy.